Xenon-129 biosensors offer exciting potential for the simultaneous magnetic resonance imaging (MRI) of multiple frequency-resolved biomolecular targets. In addition to being a relatively abundant isotope of a non-toxic noble gas, the xenon-129 nucleus is spin-½ and can be laser-polarized to increase nuclear magnetic resonance (NMR) signals more than 10,000-fold. The polarizability of the xenon electron cloud imparts considerable environmental sensitivity to the chemical shift of the 129Xe nucleus, producing a nearly 300 ppm 129Xe NMR chemical shift window in common solvents. This sensitivity facilitates the simultaneous detection of monatomic 129Xe in different chemical environments. Biosensors exploiting this property have been generated by attaching a xenon-binding cryptophane-A moiety to protein-specific ligands such as biotin or protease-specific peptides. Cryptophane-based biosensors can be spectrally and spatially resolved in MR imaging and the cryptophane has been shown to be a competent xenon binder under near-physiological conditions.
Accordingly, there is a need in the art for improved xenon-binding host molecules in both organic and aqueous phase.